N-cadherin in osteolineage cells is not required for maintenance of hematopoietic stem cells

Blood. 2012 Jul 12;120(2):295-302. doi: 10.1182/blood-2011-09-377457. Epub 2012 Feb 9.

Abstract

There is evidence suggesting that N-cadherin expression on osteoblast lineage cells regulates hematopoietic stem cell (HSC) function and quiescence. To test this hypothesis, we conditionally deleted N-cadherin (Cdh2) in osteoblasts using Cdh2(flox/flox) Osx-Cre mice. N-cadherin expression was efficiently ablated in osteoblast lineage cells as assessed by mRNA expression and immunostaining of bone sections. Basal hematopoiesis is normal in these mice. In particular, HSC number, cell cycle status, long-term repopulating activity, and self-renewal capacity were normal. Moreover, engraftment of wild-type cells into N-cadherin-deleted recipients was normal. Finally, these mice responded normally to G-CSF, a stimulus that mobilizes HSCs by inducing alterations to the stromal micro-environment. In conclusion, N-cadherin expression in osteoblast lineage cells is dispensable for HSC maintenance in mice.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Base Sequence
  • Bone Diseases, Metabolic / etiology
  • Cadherins / deficiency
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Cell Lineage / genetics
  • Cell Lineage / physiology
  • Female
  • Fluorouracil / pharmacology
  • Granulocyte Colony-Stimulating Factor / pharmacology
  • Hematopoiesis / genetics
  • Hematopoiesis / physiology
  • Hematopoietic Stem Cell Mobilization
  • Hematopoietic Stem Cells / cytology*
  • Hematopoietic Stem Cells / drug effects
  • Hematopoietic Stem Cells / metabolism*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Osteoblasts / cytology*
  • Osteoblasts / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Recombinant Proteins / pharmacology

Substances

  • Cadherins
  • Cdh2 protein, mouse
  • RNA, Messenger
  • Recombinant Proteins
  • Granulocyte Colony-Stimulating Factor
  • Fluorouracil